Dose-to-target of etanercept treatment:
a dose-tapering randomized controlled trial in patients with juvenile idiopathic arthritis in patients age 12 years and older.

The proportion of patients with rheumatic diseases treated with biologics has
increased considerably over the last decade. As a consequence, the financial
burden for the health care system has increased enormously. Therefore, dose
reduction of biologics is currently a hot topic in rheumatology practice.
However, there is limited information about the success rate of dose tapering
or discontinuation as well as predictors of success and the risks of dose
reduction, like deterioration of disease activity and radiographic progression.
Recently, a few studies in juvenile idiopathic arthritis (JIA) on etanercept
were published but these studies have some major limitations: limited numbers
of patients with different subtypes of JIA were included and only retrospective
data were available. In addition, to our knowledge no study has been performed
in patients with JIA age 17 years or older.

To determine the proportion of patients with JIA maintaining minimal disease
activity (MDA) after dose interval prolongation of etanercept. Secondary
objectives: To study the cost-effectiveness of tapering down etanercept
treatment, to investigate whether the lowest effective etanercept dose will
reduce the risk of adverse events and to study the predictive value of serum
etanercept trough levels for successful down titration.

Randomized controlled trial: a dose-to-target step-down treatment strategy of
etanercept which consists of 2 phases, including all suitable JIA patients
currently treated in our institute. Main study parameters: Minimal Disease
Activity will define whether a patient is suitable for inclusion and
randomisation. Definition of Minimal Disease Activity (MDA) is according to the
JADAS cut-off values for minimal disease activity. Patients should be in MDA at
baseline and clinically in low disease activity according to the treating
rheumatologist, for at least 6 months. Etanercept serum concentrations, disease
activity, functional ability, quality of life and cost related parameters will
be measured during follow-up.

Patients with Minimal Disease Activity at baseline and with clinically low
disease activity for at least 6 months during etanercept treatment will be
approached for participation. After inclusion, etanercept dose interval will be
prolonged to once every 2 weeks (phase 1). Patients will be followed for 6
months. Thereafter, the second phase of this study starts, in which patients,
who are still in a state of minimal disease activity, will discontinue
etanercept. Patients will be followed for an additional 6 months. Thereafter,
patients of the control arm in whom disease activity is low after 6 months of
etanercept dose reduction, etanercept will also be discontinued.

We hypothesize that patients with Minimal Disease Activity will remain in a
state of Minimal Disease Activity after dose interval prolongation of
etanercept, however, an increased disease activity risk can not be excluded,
especially in patients discontinuing etanercept.